DDESC: Dragon database for exploration of sodium channels in human

<p>Abstract</p> <p>Background</p> <p>Sodium channels are heteromultimeric, integral membrane proteins that belong to a superfamily of ion channels. The mutations in genes encoding for sodium channel proteins have been linked with several inherited genetic disorders such as febrile epilepsy, Brugada syndrome, ventricular fibrillation, long QT syndrome, or channelopathy associated insensitivity to pain. In spite of these significant effects that sodium channel proteins/genes could have on human health, there is no publicly available resource focused on sodium channels that would support exploration of the sodium channel related information.</p> <p>Results</p> <p>We report here Dragon Database for Exploration of Sodium Channels in Human (DDESC), which provides comprehensive information related to sodium channels regarding different entities, such as "genes and proteins", "metabolites and enzymes", "toxins", "chemicals with pharmacological effects", "disease concepts", "human anatomy", "pathways and pathway reactions" and their potential links. DDESC is compiled based on text- and data-mining. It allows users to explore potential associations between different entities related to sodium channels in human, as well as to automatically generate novel hypotheses.</p> <p>Conclusion</p> <p>DDESC is first publicly available resource where the information related to sodium channels in human can be explored at different levels. This database is freely accessible for academic and non-profit users via the worldwide web <url>http://apps.sanbi.ac.za/ddesc</url>.</p

“Lest we forget” : An overview of Australia’s response to the recovery and identification of unrecovered historic military remains

Peer reviewedPostprin

Histological basis of laminar MRI patterns in high resolution images of fixed human auditory cortex

Functional magnetic resonance imaging (fMRI) studies of the auditory region of the temporal lobe would benefit from the availability of image contrast that allowed direct identification of the primary auditory cortex, as this region cannot be accurately located using gyral landmarks alone. Previous work has suggested that the primary area can be identified in magnetic resonance (MR) images because of its relatively high myelin content. However, MR images are also affected by the iron content of the tissue and in this study we sought to confirm that different MR image contrasts did correlate with the myelin content in the grey matter and were not primarily affected by iron content as is the case in the primary visual and somatosensory areas. By imaging blocks of fixed post-mortem cortex in a 7 Tesla scanner and then sectioning them for histological staining we sought to assess the relative contribution of myelin and iron to the grey matter contrast in the auditory region. Evaluating the image contrast in T2*-weighted images and quantitative R2* maps showed a reasonably high correlation between the myelin density of the grey matter and the intensity of the MR images. The correlation with T1-weighted phase sensitive inversion recovery (PSIR) images was better than with the previous two image types, and there were clearly differentiated borders between adjacent cortical areas in these images. A significant amount of iron was present in the auditory region, but did not seem to contribute to the laminar pattern of the cortical grey matter in MR images. Similar levels of iron were present in the grey and white matter and although iron was present in fibres within the grey matter, these fibres were fairly uniformly distributed across the cortex. Thus we conclude that T1- and T2*-weighted imaging sequences do demonstrate the relatively high myelin levels that are characteristic of the deep layers in primary auditory cortex and allow it and some of the surrounding areas to be reliably distinguished

CD1a expression in psoriatic skin following treatment with propylthiouracil, an antithyroid thioureylene

BACKGROUND: The antithyroid thioureylenes, propylthiouracil (PTU) and methimazole (MMI), are effective in the treatment of patients with plaque psoriasis. The mechanism of action of the drugs in psoriasis is unknown. Since the drugs reduce circulating IL-12 levels in patients with Graves' hyperthyroidism, the effect of propylthiouracil on CD1a expression in psoriatic lesions was examined in biopsy samples of patients with plaque psoriasis. CD1a is a marker of differentiated skin antigen presenting cells (APC, Langerhans cells). Langerhans cells and skin monocyte/macrophages are the source of IL-12, a key cytokine involved in the events that lead to formation of the psoriatic plaque. METHODS: Biopsy specimens were obtained from six patients with plaque psoriasis who were treated with 300 mg propylthiouracil (PTU) daily for three months. Clinical response to PTU as assessed by PASI scores, histological changes after treatment, and CD1a expression in lesional skin before and after treatment were studied. RESULTS: Despite significant improvement in clinical and histological parameters the expression of CD1a staining cells in the epidermis did not decline with propylthiouracil treatment. CONCLUSIONS: It appears that the beneficial effect of propylthiouracil in psoriasis is mediated by mechanisms other than by depletion of skin antigen-presenting cells

Lead(II) coordination polymers driven by pyridine-hydrazine donors : from anion-guided self-assembly to structural features

In this work, we report extensive experimental and theoretical investigations on a new series of PbII coordination polymers exhibiting extended supramolecular architectures, namely [Pb2(LI)(NCS)4]n (1), [Pb(HLII)I2]n (2), [Pb(LIII)I]n (3) and [Pb(HLIV)(NO3)2]n·nMeOH (4), which were self-assembled from different PbII salts and various pyridine-hydrazine based linkers, namely 1,2-bis(pyridin-3-ylmethylene)hydrazine (LI), (pyridin-4-ylmethylene)isonicotinohydrazide (HLII), 1-(pyridin-2-yl)ethylidenenicotinohydrazide (HLIII) and phenyl(pyridin-2-yl)methylenenicotinohydrazide (HLIV), respectively. It is recognized that the origin of self-assembling is fundamentally rooted in a dual donor (6s2/6p0 hybridized lone electron pair) and electrophilic behaviour of PbII. This allows production of extended topologies from a 1D polymeric chain in 4 through a 2D layer in 2 to the 3D frameworks in 1 and 3, predominantly due to the cooperative action of both covalent and non-covalent tetrel interactions of the overall type Pb-X (X = O, N, S, I). Counterintuitively, the latter, seemingly weak interactions, have appeared to be even stronger than the typical covalent bonds due to the presence of a bunch of supportive London dispersion dominated contacts: ππ, Lpπ, C-HO, C-HI, C-HH-C as well as more typical mainly electrostatically driven N-HO or N/O-HO hydrogen bonds. It is revealed that the constituting generally strong tetrel type Pb-X (X = O, N, S, I) bonds, though dominated by a classic Coulomb term, are therefore characterized by a very important London dispersion constituent, extremely strong relativistic effects and the two way dative-covalent Pb ↔ X electron charge delocalization contribution as revealed by the Extended Transition State Natural Orbital for Chemical Valence (ETS-NOCV) charge and energy decomposition scheme. It unravels that the pyridine-hydrazine linkers are also excellent London dispersion donors, and that together with the donor-acceptor properties of the heavy (relativistic) PbII atoms and nucleophilic counterions lead to extended self-assembling of 1-4

The North American tree-ring fire-scar network

Fire regimes in North American forests are diverse and modern fire records are often too short to capture important patterns, trends, feedbacks, and drivers of variability. Tree-ring fire scars provide valuable perspectives on fire regimes, including centuries-long records of fire year, season, frequency, severity, and size. Here, we introduce the newly compiled North American tree-ring fire-scar network (NAFSN), which contains 2562 sites, >37,000 fire-scarred trees, and covers large parts of North America. We investigate the NAFSN in terms of geography, sample depth, vegetation, topography, climate, and human land use. Fire scars are found in most ecoregions, from boreal forests in northern Alaska and Canada to subtropical forests in southern Florida and Mexico. The network includes 91 tree species, but is dominated by gymnosperms in the genus Pinus. Fire scars are found from sea level to >4000-m elevation and across a range of topographic settings that vary by ecoregion. Multiple regions are densely sampled (e.g., >1000 fire-scarred trees), enabling new spatial analyses such as reconstructions of area burned. To demonstrate the potential of the network, we compared the climate space of the NAFSN to those of modern fires and forests; the NAFSN spans a climate space largely representative of the forested areas in North America, with notable gaps in warmer tropical climates. Modern fires are burning in similar climate spaces as historical fires, but disproportionately in warmer regions compared to the historical record, possibly related to under-sampling of warm subtropical forests or supporting observations of changing fire regimes. The historical influence of Indigenous and non-Indigenous human land use on fire regimes varies in space and time. A 20th century fire deficit associated with human activities is evident in many regions, yet fire regimes characterized by frequent surface fires are still active in some areas (e.g., Mexico and the southeastern United States). These analyses provide a foundation and framework for future studies using the hundreds of thousands of annually- to sub-annually-resolved tree-ring records of fire spanning centuries, which will further advance our understanding of the interactions among fire, climate, topography, vegetation, and humans across North America

Relapse to smoking during unaided cessation: Clinical, cognitive, and motivational predictors

Rationale: Neurobiological models of addiction suggest that abnormalities of brain reward circuitry distort salience attribution and inhibitory control processes, which in turn contribute to high relapse rates. Objectives: To determine whether impairments of salience attribution and inhibitory control predict relapse in a pharmacologically unaided attempt at smoking cessation. Methods: 141 smokers were assessed on indices of nicotine consumption / dependence (e.g. the FTND, cigarettes per day, salivary cotinine), and three trait impulsivity measures. After overnight abstinence they completed experimental tests of cue reactivity, attentional bias to smoking cues, response to financial reward, motor impulsiveness, and response inhibition (antisaccades). They then started a quit attempt with follow-up after 7 days, 1 month, and 3 months; abstinence was verified via salivary cotinine levels ≤ 20ng/ml. Results: Relapse rates at each point were 52.5%, 64% and 76.3%. The strongest predictor was pre-cessation salivary cotinine; other smoking / dependence indices did not explain additional outcome variance and neither did trait impulsivity. All experimental indices except responsivity to financial reward significantly predicted one week outcome. Salivary cotinine, attentional bias to smoking cues and antisaccade errors explained unique as well as shared variance. At one and three months, salivary cotinine, motor impulsiveness and cue reactivity were all individually predictive; the effects of salivary cotinine and motor impulsiveness were additive. Conclusions: These data provide some support for the involvement of abnormal cognitive and motivational processes in sustaining smoking dependence and suggest that they might be a focus of interventions, especially in the early stages of cessation. Dawkins L, Powell JH, Pickering AD, Powell JF, and West RJ (2009) Addiction 104, 850-

Individual differences in reward prediction error: Contrasting relations between feedback-related negativity and trait measures of reward sensitivity, impulsivity and extraversion

Medial-frontal negativity occurring ~200-300 msec post-stimulus in response to motivationally salient stimuli, usually referred to as feedback related negativity (FRN), appears to be at least partly modulated by dopaminergic-based reward prediction error (RPE) signaling. Previous research (e.g. Smillie, Cooper & Pickering, 2011) has shown that higher scores on a putatively dopaminergic-based personality trait, Extraversion, were associated with a more pronounced difference wave contrasting unpredicted non-reward and unpredicted reward trials on an associative learning task. In the current study, we sought to extend this research by comparing how trait measures of Reward Sensitivity, Impulsivity and Extraversion related to the FRN using the same associative learning task. A sample of healthy adults (N = 38) completed a battery of personality questionnaires, before completing the associative learning task while EEG was recorded. As expected, FRN was most negative following unpredicted non-reward. A difference wave contrasting unpredicted non-reward and unpredicted reward trials was calculated. Extraversion, but not measures of Impulsivity, had a significant association with this difference wave. Further, the difference wave was significantly related to a measure of anticipatory pleasure, but not consummatory pleasure. These findings provide support for the existing evidence suggesting that variation in dopaminergic functioning in brain ‘reward’ pathways may partially underpin associations between the FRN and trait measures of extraversion and anticipatory pleasure

Households’ vulnerability from trade in Vietnam

This paper assesses vulnerability from trade in Vietnam by presenting an extended version of Ligon and Schechter’s (2003) Vulnerability as low Expected Utility (VEU) measure. It uses the Vietnam Household Living Standard Surveys (VHLSS) panel data covering the period 2002–06. The empirical results show that risk-induced vulnerability and heterogeneity in trade exposure matter in determining household overall vulnerability and that this is not linked to the actual manifestation of shocks. Although it does not represent, by any means, an argument against free trade, this work is relevant for policymaking since it contributes to deepen our knowledge on the subtle links between trade openness and vulnerability and informs us about suitable instruments to accompany it